IFNα 对准备停药、处于深度分子学缓解的慢性髓系白血病患者 T 细胞和 NK 细胞的免疫调节作用

A deep and stable molecular response (DMR) is a prerequisite for a successful treatment-free remission (TFR) in chronic myeloid leukemia (CML). In order to better identify and analyze potential candidates of successful TFR, we examined the phenotypic and functional host immune compartment in DMR patients who had received TKI treatment only (TKI-only) or had been previously treated with interferon-alpha (IFN + TKI) or had received IFN treatment only (IFN -only). The T/NK-cell subset distribution, NK- and T-cell cytokine production, activation and maturation markers were measured in 44 patients in DMR treated with IFN only (9), with IFN + TKI (11) and with TKI-only (24).

IFN + TKI and TKI-only groups were eligible to TKI discontinuation according to the NCCN and ESMO guidelines (stable MR4 for more than two years). In IFN -treated patients, we documented an increased number of lymphocytes capable of producing IFN and TNF compared to the TKI-only group.

In INF + TKI patients, the percentage of NKG2C expression and its mean fluorescence intensity were significantly higher compared to the TKI-only group and to the INF -only group in the CD56dim/CD16+ NK cell subsets (INF + TKI vs. TKI-only p = 0. 041, p = 0. 037; INF + TKI vs. INF -only p = 0. 03, p = 0. 033, respectively).

Furthermore, in INF -only treated patients, we observed an increase of NKp46 MFI in the CD56bright/CD16- NK cell subset that becomes significant compared to the INF + TKI group ( p = 0. 008).

Our data indicate that a previous exposure to IFN substantially and persistently modified the immune system of CML patients in memory T lymphocytes, differentiated NKG2C+ "long-lived" NK cells responses, even years after the last IFN contact.